D-mannitol, a kind of hexitol, is widely used in a variety of foods, base for various medicines or excipient for tablets, powder, etc. thanks to its characteristics such as excellent stability, usually in inodorous white crystalline powder, mild sweet taste equivalent to 60 to 70% of sucrose, lower calorie than sucrose or glucose, safety to human body, etc.
Mannitol takes the form of fine needle-like crystals, when crystallized from water solution, and is poorly fluid as granulated. In addition, mannitol, often marketed and used in the form of fine crystalline powder commonly packed in kraft bag, is likely to get consolidated, when distributed or stocked, significantly losing its commercial importance.
Moreover, other problems are found e.g. in the fact that tablets, made from crystalline mannitol just as crystallized from water solution and directly compressed, are easily collapsed due to low hardness or it is difficult to be compressed successively as disturbed by capping, sticking etc. during the process of compressing.
To overcome the above drawbacks of crystalline mannitol, various solutions have been so far proposed.
One of the solutions is to work it into balls in order to improve fluidity, while avoiding consolidating or collapsing, as reported with some examples.
Japanese Patent No. 3447042 discloses “A manufacturing process of spherical particles having an aspect ratio of 1.2 or less, apparent density of 0.65 g/ml or more in aggregate, an angle of repose equal to or less than 35 degrees and abrasiveness of 1.0 or less, wherein particles containing 95% by weight or more water-soluble single matter having a viscosity of 10 cP or less in saturated water solution are made”, referring to D-mannitol as an example of “water-soluble single matter”.
Japanese Patent No. 3491887 discloses “A manufacturing process of sugar alcohol granulated aggregate, to be subjected to direct compression processing, containing 95% by weight or more particles of 710 μm or less, 50% by weight or more particles within a range of 75 to 710 μm, having an apparent density of 0.5 g/ml or more, an angle of repose equal to or less than 40 degrees, wherein powder containing 95% or more by weight sugar alcohol is put into a fluidized granulation coating device, while supplied with fluidized air into the container to fluidize the powder, spraying sugar alcohol water solution to make particles, followed by sifting the granulated matters through a sieve”, referring to D-mannitol as an example of “sugar alcohol”.
Japanese Patent No. 3910939 discloses “Spherical particles, made of particles containing 95% by weight or more water-soluble single matter, having an aspect ratio of 1.2 or less, apparent density of 0.65 g/ml or more in aggregate, an angle of repose equal to or less than 35 degrees, characterized in that a) the water-soluble single matter is selected as one of the group consisting of sugar alcohol, vitamin C and sodium chloride; b) saturated water solution of the water-soluble single matter has a viscosity of 10 cP or less in the range of 25 to 45° C.; and c) the spherical particles have abrasiveness of 1.0% or less”, referring to D-mannitol as an example of “sugar alcohol”.
However, granulation is the only processing method adopted in all of the above 3 patents, leaving various problems unsolved.
Granulation consists in coagulating one after another the surrounding mannitol particles around the core mannitol, using appropriate solvent and solution, as needed, drying the surrounding to precipitate solid ingredients, or combining these methods, anyway to make the raw material powder grow into bigger and bigger clusters.
The problem of the above is that it is especially difficult and costly to form, by granulation, highly spherical particles having a fine diameter from needle-like crystals like crystalline mannitol, used as raw material powder, failing to respond to the needs of light and fine particles, since the particles thus obtained are heavy as charged with crystals dense inside the particles and likely to have a large particle diameter.
On the other hand, Japanese Laid-Open Patent No. 61-85330 discloses a manufacturing process of an excipient for a direct compressing tablet characterized in that D-mannitol is sprayed and dried. However, the Official Gazette describes the manufacturing conditions quite roughly, only referring to use of 25 to 33% by weight D-mannitol water solution and spraying and drying at discharging temperatures of 120 to 140° C., without any intention to obtain spherical powder. The photo of actually obtained powder as shown in FIG. 1 in the Official Gazette shows the distorted shape, far from sphericity.    [Patent Document 1] Specification of Japanese Patent No. 3447042    [Patent Document 2] Specification of Japanese Patent No. 3491887    [Patent Document 3] Specification of Japanese Patent No. 3910939    [Patent Document 4] Japanese Laid-Open Patent No. 61-85330